Method of inhibiting HIV-1 binding to genital epithelia using V3 loop-specific peptides and GP340-specific antibodies

Abstract

This invention relates to methods compositions and devices for inhibiting infection of a subject's host cell by HIV. Specifically, the invention relates to methods and compositions capable of inhibiting the binding and subsequent infection by HIV of a host cell through the inhibition of the interaction between gp-340 expressed on the cell surface and V3 loop on the HIV envelope and devices comprising these compositions.

What is claimed is: 
     
       1. A method of inhibiting binding of a human immunodeficiency virus (HIV) to a genital tract tissue in a subject, comprising the step of: contacting the genital tract with an effective amount of an agent capable of inhibiting the binding between immunodeficiency virus and gp-340, wherein said agent inhibits binding of gp-120 with gp-340 and is selected from the group consisting of a V3 loop-specific peptide and an antibody or functional fragment thereof, wherein the antibody is a monoclonal antibody (mAb), a polyclonal antibody (pAb), or a humanized antibody specific against gp-340, wherein the V3 loop-specific peptide comprises a contiguous gp-120 V3 loop sequence at least 15 amino acid long, and wherein the antibody against gp-340 is specific for a Lewis Y (Le Y ) epitope. 
     
     
       2. The method of  claim 1 , wherein the V3 loop-specific peptide comprises the amino acid sequence set forth in SEQ ID NO. 1, SEQ ID NO. 2 or a combination thereof. 
     
     
       3. The method of  claim 1 , wherein said fragment is Fc, Fab, F(ab′)2, scFv or a combination thereof. 
     
     
       4. The method of  claim 1 , further comprising the step of administering to the subject an effective amount of a soluble gp-340, gp-340 mimetic or a combination thereof. 
     
     
       5. The method of  claim 1 , further comprising the step of administering to the subject an effective amount of 2,5-dimethoxy-substituted 5-bromopyridyl thiourea (PHI-236), nonoxynol-9 or a combination thereof. 
     
     
       6. A method of inhibiting attachment of a human immunodeficiency virus (HIV) to a host cell, comprising the step of contacting a gp340 protein expressed on the host cell with an agent capable of inhibiting attachment, wherein said agent inhibits binding of gp-120 with gp-340 and is a V3 loop-specific peptide or a gp340-specific antibody or a functional fragment thereof, wherein said antibody is a monoclonal antibody (mAb), a polyclonal antibody (pAb), or a humanized antibody, wherein the V3 loop-specific peptide comprises a contiguous gp-120 V3 loop sequence at least 15 amino acid long, and wherein the antibody against gp-340 is specific for a Lewis Y (Le Y ) epitope. 
     
     
       7. The method of  claim 6 , wherein said fragment is Fc, Fab, F(ab′)2, scFv or a combination thereof. 
     
     
       8. The method of  claim 6 , wherein the host cell is a vaginal, an endocervical or an ectocervical primary epithelial cell. 
     
     
       9. The method of  claim 6 , wherein the V3 loop-specific peptide comprises the amino acid sequence set forth in SEQ ID NO. 1, SEQ ID NO. 2 or their combination. 
     
     
       10. The method of  claim 6 , further comprising contacting the virus with 2,5-dimethoxy-substituted 5-bromopyridyl thiourea (PHI-236), nonoxynol-9, or a combination thereof.